Progress in the Development of Alternative Pharmaceutical Formulations of Taxanes

Byline: Bastiaan Nuijen (1), Marjan Bouma (1), Jan H.M. Schellens (1), Jos H. Beijnen (1) Keywords: taxanes; paclitaxel; docetaxel; alternative formulation; co-solvents; surfactants; emulsions; micro-encapsulation systems; liposomes; cyclodextrines; prodrugs Abstract: The currently available taxanes paclitaxel(Taxol(r)) and docetaxel(Taxotere(r)) are clinically effectiveagainst advanced breast, ovarian andnon-small cell lung cancer. Due to theirlow aqueous solubility, both taxanes poseddifficulties to the pharmaceuticalscientists with respect to the developmentof an intravenous dosage form. At present,paclitaxel is formulated in a mixture of50:50% (v/v) Cremophor EL and dehydratedethanol. However, this formulation vehicleis associated with a number ofpharmacological, pharmacokinetic andpharmaceutical concerns amongst whichserious hypersensitivity reactions. Thisreview deals with the attempts made intothe development of alternative dosage formsof paclitaxel devoid of the CremophorEL/ethanol excipients and potential futuretaxane formulations. Author Affiliation: (1) Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands Article History: Registration Date: 11/10/2004